Sampling device and method for obtaining samples of internal boby substancesand method for producing a sampling device

ABSTRACT

The present invention relates to a sampling device for obtaining samples of internal body substances in the digestive system of humans or animals. The sampling device has the shape of a swallowable capsule ( 2 ) which allows a sample of the body substance ( 26 ) to enter the capsule through an inlet opening ( 18 ) which is opened in a predetermined position of the digestive tract following contact with the body substance to be collected. The capsule ( 2 ) comprises a capsule wall ( 3 ) comprising said inlet opening ( 18 ), which initially is sealed and, when the patient has swallowed the capsule ( 2 ), is opened in said predetermined position following contact with the body substance to be collected, an inner chamber ( 5 ), defined by said capsule wall ( 3 ) and disposed to preserve a vacuum or substantial under pressure when the inlet opening ( 18 ) is sealed, and a blocking member ( 12 ) disposed in the inner chamber ( 5 ) adjacent to the inlet opening ( 18 ) in the capsule wall ( 3 ). The blocking member ( 12 ) is elastic and has a configuration, such that, when the inlet opening ( 18 ) has been opened following contact with said body substance, the blocking member ( 12 ) has a flow permitting configuration which admits a flow of body substance into the inner chamber ( 5 ) as long as a there is a pressure difference between the inner chamber ( 5 ) and the external environment of the capsule ( 2 ) and a flow preventing configuration which blocks the inlet opening ( 18 ) from the inside of the chamber ( 5 ) when said pressure difference has been equalised by the flow of body substance into the capsule ( 2 ).  
     The invention also relates to a sampling method for obtaining samples of internal body substances and a method for producing the sampling device.

FIELD OF THE INVENTION

[0001] The present invention relates to a sampling device for obtainingsamples of internal body substances in the digestive system of humans oranimals. The sampling device has the shape of a swallowable capsulewhich allows a sample of the body substance to enter the capsule throughan inlet opening which is opened in a predetermined position of thedigestive tract following contact with the body substance to becollected. The invention also relates to a sampling method for obtainingsamples of internal body substances and a method for producing thesampling device.

BACKGROUND OF THE INVENTION

[0002] Examination of internal body substances, gases or solid particlesin the digestive system or the gastrointestinal tract in the human oranimal body provides essential medical information for diagnosing andtreatment. Examination of a sample of the gastric fluid of a patientprovides important information of pH, acid contents, abdominal enzymeactivity as well as information for diagnosing gastric ulcer andgastritis, cancer and tumour diseases, etc. A gastroscopic examinationgives the physician who is treating a patient important information andplays a great role for a diagnosis. These intubation examinations arethus used extensively. A gastroscopic examination, in which a tube,having a diameter of a little finger, is inserted into the patient'smouth or nose, through the oesophagus and to the gastrointestinalsystem, is difficult to perform and demands the assistance of aphysician. For the patient, the intubation of the digestive tract usingthese methods is a very unpleasant intervention, both physically andpsychologically, especially during the insertion of the tube and alsowhen it is pulled out. The intubation demands that the patient is givena local anaesthetic and in some instances even tranquilliser or ageneral anaesthetic to overcome the stress to which the patient issubjected. The incubation examination methods described above aredisadvantageous since they are very time-consuming for a qualifiedphysician and thus expensive and a very unpleasant intervention for thepatient.

[0003] The application of a swallowable capsule for automaticallyobtaining samples of internal gastric fluids has been proposed as analternative examination method and is described in U.S. Pat. No.4,481,952. The capsule is equipped with mechanisms, which control theopening and closing of the capsule. The mechanisms are blocked byblocking mechanisms, including a mass which is dissolved after a shorttime following contact with the gastric fluid. The opening of thecapsule, the collection of the sample and the reclosing of the capsuletakes place automatically in the patient's stomach. The describedsampling device is advantageous in many ways. However, it has proved tofunction unsatisfactorily and has therefore not been widely used. Thedescribed capsule is expensive, is mechanically complicated andcomprises mutually movable parts, mostly metal parts. As a consequence,the parts tend to jam, fluids tend to leak between the parts, frictionforces between the parts must be overcome, e.g. by spring forces, andmetal parts, such as springs, may loosen in the gastrointestinal tractcausing injuries to the patients.

BASIC IDEA OF THE INVENTION

[0004] The object of the present invention is to solve theabove-mentioned problems of the prior art by providing a sampling devicewhich operates automatically in the system of a patient and which issimple, inexpensive to produce, reliable and easy to use.

[0005] This object is achieved in accordance with the invention in asampling device and a method for obtaining samples and a method forproducing a sampling device as described above and with thecharacterising features as defined in the attached claims.

[0006] In accordance with the invention, a sampling device forautomatically obtaining samples of internal body substances is shaped asa capsule such that it may be swallowed by the patient without anystress or pain. In a predetermined position in the digestive system, thecapsule is opened and a sample of the body substance is aspiratedthrough an inlet opening into the capsule by the force of a vacuum orsubstantial underpressure in the capsule. When a predetermined volume ofthe sampling substance has been collected in the capsule, i.e. thecapsule is filled, the inlet opening is automatically closed, sealing itfrom the inside of the capsule, such that the sample remains in thecapsule. The capsule with the collected sample is fed through thegastrointestinal tract of the digestive system and, still with no stressor pain for the patient out of the human body together with the feciesin a normal manner. The capsule with the collected sample subsequentlyis sent or handed over to a medical institution or laboratory, where thesample is evacuated from the capsule to be analysed.

[0007] The sampling device according to the invention is simple and ismade of a few essential parts. Just one of these part, the elasticblocking member, is resiliently movable between a flow permittingconfiguration and a flow preventing configuration and is affected byforces ensuing from the pressure difference between the outside and theinside of the capsule. Through this constructional feature of theclosing member, a reliable, simple and inexpensive sampling device isachieved with no metal or mutually movable parts that may jam, leak orcome loose in the system and cause injuries to the patient. Through theproduction method according to the invention a vacuum or substantialunderpressure is created in the capsule and this vacuum or substantialunderpressure exerts sufficient forces for opening the closing memberand for aspiration of a sample of a body substance into the capsule.Through the sampling method according to the invention, the collectionof internal body substances can be performed extremely simple andinexpensive and the examination may be carried out without any pain,stress or discomfort to the patient.

SHORT DESCRIPTION OF THE DRAWINGS

[0008] The invention will be described more in detail below withreference to the attached drawings, in which:

[0009] FIG. 1 is a sectional view of a sampling device according to afirst embodiment of the invention, in a first closed and sealed state,

[0010] FIG. 2 shows the sampling device of FIG. 1 in a second, openstate, and in a flow permitting configuration with the body substanceflowing into the device,

[0011] FIG. 3 shows the sampling device of FIG. 1 in a third, reclosedstate, and in a flow preventing configuration in which the bodysubstance has filled up the sampling device,

[0012] FIG. 4 shows the sampling device of FIG. 1 in a fourth,evacuating state, in which the sample of body substance is evacuatedfrom the capsule to be analysed,

[0013] FIG. 5 is a sectional view of a sampling device according to asecond embodiment of the invention, in a first closed and sealed state,

[0014] FIG. 6 shows the sampling device of FIG. 5 from above,

[0015] FIG. 7 shows an enlarged scale perspective view of an embodimentof the blocking member, and

[0016] FIG. 8 shows a schematic elevation view of the vacuum chamber.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

[0017] FIG. 1 is a sectional view of a sampling device according to theinvention, said device being designed to obtain samples of internal bodysubstances, such as body fluids, in the digestive tract of a patient. InFIG. 1, the sampling device is shown in a first closed and sealed state,in which it is handed over to be swallowed by a patient, from whom asample of an internal body fluid, such as the gastric fluid in thestomach, for example, shall be collected.

[0018] The sampling device has the shape of a capsule 2, such as aconventional pharmaceutical capsule, and is thus suitable for ingestion.The capsule 2 is preferably elongated and has rounded end portions andpreferably a circular or oval-shaped cross-section. The capsule 2comprises an inner chamber 5 defined by a capsule wall 3.

[0019] The capsule 2, preferably made of a thermoplastic material or anyother suitable material, is made of at least two capsule members, a capmember 4 and a body member 6, said cap 4 and body 6 members beingpermanently joined to each other, as will be described more in detailbelow. The inner chamber 5 of the capsule 2 may comprise a filter 10,preferably clamped in the capsule 2 between the cap member 4 and thebody member 6, to filtrate the body fluid sample, when required.

[0020] A blocking member 12 in the capsule is shown in an enlarged viewin FIG. 7. The inner blocking member 12, such as a membrane valve, madeof a flexible, elastic and resilient rubbery material, has a circularfixation edge 19 which is clamped in the capsule 2 between the capmember 4 and the body member 6. In the embodiment as shown, the blockingmember 12 has the form of a bulb and has at least one, preferablyseveral, apertures 16 arranged in the slanted side of the bulb. In theclosed and sealed state, as shown in FIG. 1, the blocking member 12bears on a preferably circular contact surface 22 on the inside of thecapsule wall 3. The contact or sealing area 17 on the blocking member 12is shown between the dashed lines in FIG. 7. Through the shape of theblocking member and the resilience of the material, the blocking member12 bears on the contact surface 22 with a bearing pressure.

[0021] The circular contact surface 22, formed as a bulge-formed lining,is arranged on the inside of the capsule wall 3 and extends around aninlet opening 18 in said wall. In the closed and sealed state of thecapsule as shown in FIG. 1, the inlet opening 18 is sealed by a plug 20.The plug 20 in the capsule 2 is made of a material which is chosendepending on the application of the capsule, i.e. the specific bodyfluid to be collected. The plug 20 is dissolved after a short period oftime in the body fluid in question, in the embodiment as described, thedigestive fluid. Thus, the material of the plug 20 is adapted to thespecific fluid or substance in the external environment of the capsulein the position in the body system where the sample is collected. Thematerial of the plug 20 is, for example, gelatine, molten sugar, salt,glue, organic edible materials or any other suitable material.Alternatively, the plug 20 can be made of two or more layers ofdifferent materials, which dissolve gradually upon contact withdifferent substances in the external environment of the capsule 2 duringits passage through the digestive system. The innermost layer dissolvesupon contact with body fluid to be collected by the capsule 2.

[0022] A section of the capsule wall 3, preferably in the body member 6of the capsule, is thinner and forms a notch 24. The notch 24 is usedwhen the body fluid sample in the inner chamber 5 shall be evacuatedfrom the capsule, as will be described more in detail with reference toFIG. 4.

[0023] In the inner chamber 5 of the capsule, defined by the capsulewall 3 and the plug 20, a vacuum or substantial underpressure prevailsas long as the capsule 2 is in the closed and sealed state as shown inFIG. 1.

[0024] When an examination of a body fluid in the digestive system isrequired, the patient swallows the capsule 2, e.g. the capsule as shownin FIG. 1, without any stress or pain. The size of the capsule 2 mayvary depending on the volume of body fluid required for the examinationand analysis. A suitable size of a capsule which is easy to swallow has,for example, a length of about 25 mm and a width of about 10 mm.

[0025] In FIG. 2, the inlet opening 18 of the capsule 2 has been opened.When the capsule is in the state as shown in FIG. 2, the capsule haspreviously been swallowed by the patient, has passed the oesophagus andhas entered into the stomach. During the passage of the capsule 2 fromthe mouth to the position in the system of the patient in which thesample shall be collected, the patient feels no more discomfort than hefeels when he swallows an ordinary pharmaceutical capsule, i.e. adiscomfort which is principally non-existing.

[0026] When the plug 20 has been dissolved, as shown in FIG. 2, theinlet opening 18 is open. A suction effect is generated by the pressuredifference between the external environment of the capsule 2 and theinner chamber 5 in which a vacuum or substantial underpressure prevails.This suction effect forces the resilient blocking member 12 into a flowpermitting configuration, as shown in FIG. 2. The body fluid 26 in theexternal environment of the capsule flows into the inlet opening 18 andexerts a pressure on the resilient and elastic, self-sealing blockingmember 12, such that a fluid passage into the chamber 5 is openedbetween the contact surface 22 and the blocking member 12. The bodyfluid 26 flows further through the apertures 16 in the blocking member12, through the filter 10, if any, and into the inner chamber 5, asshown in FIG. 2.

[0027] The blocking member 12 is opened and is kept open by the pressuredifference between the external environment of the capsule and the innerchamber of the capsule 2. As soon as the external and internal pressureof the capsule have been equalised and the body fluid 26 has filled upthe inner chamber 5 of the capsule, the blocking member 12 reverts to aflow preventing configuration, such that the inlet opening 18 is closedand thus the flow of body fluid from the inner chamber 5 of the capsuleis prevented. This reclosed state of the capsule is shown in FIG. 3.Since the body fluid sample fills up the inner chamber 5 of the capsuleand the fluid is prevented by the blocking member 12 to leave thechamber, the exact volume of the collected body fluid in a samplingcapsule can be predetermined. The capsule 2 with the enclosed sample ofbody fluid 26 is now fed through the gastrointestinal tract and isrecovered from the fecies of the patient.

[0028] FIG. 4 shows the recovered capsule 2 in a state in which the bodyfluid sample is evacuated from the inner chamber 5 of the capsule. Anevacuation needle 28, directly or indirectly connected to an instrumentfor examination and analysis of the body fluid sample, penetrates thenotch 24 of the chamber wall 3 and empties the inner chamber 5.

[0029] FIGS. 5 and 6 show a second preferred embodiment of theinvention, which differs from the embodiment of FIGS. 1-4 only in thatthe inlet of the capsule 2 is designed differently. Several, e.g. fourin the shown embodiment, protrusions 30 are disposed externally on thecapsule 2 at the inlet opening 18. Between the protrusions 30 laterallydirected inlet grooves 32 are formed. The protrusions 30 protect theinlet opening 18 in such a way that they prevent the capsule 2 frombeing adhered to the walls of the digestive system by the suction forcesgenerated by the internal underpressure. A free flow of body fluidthrough the inlet grooves 32 into the capsule 2 is thus always secured.

[0030] As described above, the capsule 2 consists of two members 4, 6which are permanently joined together. The members 4, 6 are preferablymade of injection-moulded thermoplastic, such as Macrolon® D forexample, which is a strong, acid resistant and transparent material andthus suitable for this purpose.

[0031] The blocking member 12 is preferably made of an elastic rubberymaterial and may be injection-moulded. The shape (see for example FIGS.3-5) and the material properties of the blocking member 12 generate theself-closing function and force the blocking member to bear on and sealoff the inlet opening 18 from the inside of the capsule 2.

[0032] The sampling device according to the invention is made of a fewparts, i.e. the cap member 4 with the plug 20, the body member 6, theblocking member 12 and, when required, also the filter 10. As shown inFIG. 7, these parts are fully or partly assembled in a vacuum chamber40, in which a vacuum or substantial underpressure is maintained bymeans of a vacuum pump (not shown) connected to the vacuum chamberthrough the vacuum hose 42. In accordance with the invention, at leastthe assembly-step that finally seals off the inner chamber 5 of thecapsule from the external environment shall be carried out in the vacuumchamber 40 in order to achieve a vacuum or substantial underpressure inthe inner chamber 5, such that sufficient suction forces are generatedto force the blocking member 12 to a flow permitting configuration andthe body fluid sample to enter and fill the capsule.

[0033] To assemble the sampling device according to the invention, theblocking member 12 and possibly the filter 10 are initially mounted inthe cap member 4 or the body member 6 and subsequently the two membersof the capsule are permanently joined together, preferably by ultrasonicwelding. The plug 20 may previously have been inserted in the inletopening 18 of the capsule. In that case, the joining of the two members4, 6 together, constitutes the assembly-step that seals off the innerchamber 5 of the capsule. Thus, at least this assembly-step must becarried out in the vacuum chamber 40.

[0034] Alternatively, when the blocking member 12 and the filter 10 havebeen mounted in either of the two members 4, 6 of the capsule 2, thesetwo members 4, 6 are permanently joined together, and then the finalsealing of the inner chamber 5 of the capsule is made by introducing theplug 20 into the inlet opening 18. Thus, at least this finalassembly-step shall be carried out in the vacuum chamber 40. The plug20, for example made of an organic glue, is quickly set when it iscooled. In the embodiment as shown in FIG. 7, the plug 20 is applied bymeans of a nozzle 44 and the glue is fed into the nozzle from thecontainer 46. In the embodiment of FIG. 7, the nozzle 44 initially isinserted into and through the inlet opening 18 of the capsule in thevacuum chamber, such that the elastic and self-closing blocking member12 is forced by the nozzle 44 to open the communication to the innerchamber 5 of the capsule and the vacuum in the vacuum chamber istransmitted to the inner chamber 5. The nozzle 44 is then withdrawn tothe position of the inlet opening 18, where the plug 20 is applied bythe nozzle 44 and sets, such that the capsule with its internal vacuumor substantial under-pressure is finally sealed. Thus, in thisassembly-step, the nozzle 44 is first used to open the blocking member12 and subsequently to apply the plug 20 of glue in the inlet opening18.

[0035] The capsule 2 may further be provided with an additional outer,covering film of gelatine or any other suitable material, which isdissolved in the digestive system. The film may be applied in order tominimise the resistance when the capsule is swallowed by the patient.

[0036] It will be understood that the invention is not restricted to theaforedescribed exemplifying embodiments thereof and that severalconceivable modifications of the invention are possible within the scopeof the following claims. For example, the plug may be formed to be fullydissolved after a predetermined time in the digestive system, such thata time delay of the opening of the inlet opening is obtained. Theelastic blocking member may have other forms and shapes and be placeddifferently in the capsule. Instead of one single inlet opening, asdescribed in the embodiments above, several adjoining inlet openings maybe provided in the capsule. In the description above, only samples ofbody fluids have been discussed. It should, however, be noted that thesampling device according to the invention also may be used to collectsamples comprising gases and/or solid particles in the digestive system.

1. A sampling device for obtaining samples of internal body substancesin the digestive tract of a patient, said device having a shape of aswallowable capsule (2) which allows a sample of the body substance toenter the capsule through at least one inlet opening (18) which isopened in a predetermined position of the digestive tract followingcontact with the body substance to be collected, characterised in thatthe capsule (2) comprises a capsule wall (3) comprising said inletopening (18), which initially is sealed and, when the patient hasswallowed the capsule (2), is opened in said predetermined positionfollowing contact with the body substance to be collected, an innerchamber (5), defined by said capsule wall (3) and disposed to preserve avacuum or substantial underpressure when the inlet opening (18) issealed, and a blocking member (12) disposed in the inner chamber (5)adjacent to the inlet opening (18) in the capsule wall (3), saidblocking member (12) being elastic and having a configuration, suchthat, when the inlet opening (18) has been opened following contact withsaid body substance, the blocking member (12) has a flow permittingconfiguration which admits a flow of body substance into the innerchamber (5) as long as a there is a pressure difference between theinner chamber (5) and the external environment of the capsule (2) and aflow preventing configuration which blocks the inlet opening (18) fromthe inside of the chamber (5) when said pressure difference has beenequalised by the flow of body substance into the capsule (2).
 2. Asampling device according to claim 1, characterised in that the inletopening (18) is sealed by a plug member (20) of a material that isdissolved following contact with said body substance.
 3. A samplingdevice according to claim 1, characterised in that the blocking member(12) consists of an elastic, self-sealing membrane, which in said flowpreventing configuration sealingly bears on the inside of the capsulewall (3), such that an outflow of the body substance in the innerchamber (5) is prevented.
 4. A sampling device according to claim 3,characterised in that the capsule (2) comprises two members, a capmember (4) and a body member (6), which are permanently joined to eachother, and that said blocking member (12) is clamped in the capsule wall(3) between said cap member (4) and said body member (6).
 5. A samplingdevice according to claim 4, characterised in that the blocking member(12) is substantially bulb-formed and has at least one laterally locatedaperture (16) for a through-flow of body substance into the innerchamber (5).
 6. A sampling device according to claim 5, characterised inthat a peripheral edge of the blocking member (12) is clamped betweensaid cap member (4) and said body member (6).
 7. A sampling deviceaccording to claim 2, characterised in that the plug member (20)consists of two or more layers of different materials and that eachlayer is dissolved in different positions in the digestive tractfollowing contact with a specific body substance.
 8. A sampling deviceaccording to claim 4, characterised in that a filter (10) is clampedbetween said cap member (4) and said body member (6) for filtrating thebody substance that flows into the inner chamber (5).
 9. A samplingdevice according to any of the preceding claims, characterised in thatprotrusions (30) are disposed externally on the capsule (2)circumferentially of the inlet opening (18), thereby forming inletgrooves (32) between the protrusions (30) for securing a free flow ofbody substance to the inlet opening (18).
 10. A sampling method forobtaining samples of internal body substances in the digestive tract ofa patient, wherein a capsule (2) is swallowed by the patient and thecapsule (2) is opened in a predetermined position of the digestive tractfollowing contact with the body substance to be collected, characterisedin that the body substance is aspirated into the capsule (2) by theforce of a vacuum or substantial underpressure inside the capsule andthat the body substance is blocked in the capsule (2) by an elastic,self-sealing blocking member (12) disposed inside the capsule (2).
 11. Asampling method according to claim 10, characterised in, that thecapsule (2) is opened to collect a sample in that a plug member (20) inan inlet opening (18) in the capsule wall (3) is dissolved followingcontact with the body substance to be collected.
 12. A sampling methodaccording to the claim 11, characterised in that said self-sealingblocking member (12) is opened to collect a sample of said body fluid bythe force of the vacuum or substantial underpressure in the capsule (2)when the plug member (20) has been dissolved.
 13. A sampling methodaccording to claim 12, characterised in that said blocking member (12)is blocking the inlet opening (18) from the inside of the capsule (2)when the vacuum or substantial underpressure in the capsule has beenequalised.
 14. A method for producing a sampling device for obtainingsamples of internal body substances in the digestive tract of a patient,said device having a shape of a swallowable capsule (2) which allows asample of the body substance to enter the capsule through at least oneinlet opening (18) in the capsule wall (3) which is opened in apredetermined position of the digestive tracts following contact withthe body substance to be collected, characterised in that the inletopening (18) in the capsule wall (3) is sealed and/or that the capsule(2), which is made of two permanently joined members (4, 6), ispermanently joined in a vacuum chamber (40) preserving a constant vacuumor substantial underpressure, such that a vacuum or substantialunderpressure is formed in an inner chamber (5) of the capsule when theinlet opening is sealed and/or when the two members (4, 6) of thecapsule are permanently joined together.
 15. A method according to claim14, characterised in that said two members (4, 6) of the capsule areinjection-moulded and are permanently joined together, preferably byultrasonic welding.
 16. A method according to claim 15, characterised inthat an blocking member (12) of the inlet opening (18) isinjection-moulded and is mounted between the two members (4, 6) of thecapsule prior to permanently joining the two members together.
 17. Amethod according to any of claims 14-16, characterised in that the inletopening (18) of the capsule is sealed off by a plug member (20),preferably made of an organic glue, and that the two members (4, 6) arejoined together in the vacuum chamber (40).
 18. A method according toany of claims 14-16, characterised in that the two members (4, 6) of thecapsule are permanently joined together and that the capsule (2) issealed off in a vacuum chamber (40) in that a plug member (20) isapplied in the inlet opening (18).
 19. A method according to claim 18,characterised in that applications means (44) for applying the plugmember (20), preferably a nozzle, is inserted into and through the inletopening (18) in the capsule wall (3), that the application means (44)forces the blocking member (12) to open, and that the application means(44) is withdrawn into the inlet opening (18) and the plug member (20),preferably of an organic glue, is applied in the opening (18) by saidapplication means (44).